Jatoi A, Murphy B R, Foster N R, Nikcevich D A, Alberts S R, Knost J A, Fitch T R, Rowland K M
Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Ann Oncol. 2006 Jan;17(1):29-34. doi: 10.1093/annonc/mdj063. Epub 2005 Nov 22.
The synergic combination of oxaliplatin and capecitabine has demonstrated activity against various gastrointestinal cancers, including colon cancer. We therefore undertook this phase II study to test this first-line combination in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia.
Forty-three patients with histologic or cytologic confirmation of the above malignancy were recruited. The cohort had Eastern Cooperative Oncology Group performance statuses of 0, 1 and 2 in 47%, 51%, and 2%, respectively. Median age was 61 years (range 32-80). All had adequate organ function. Initially, patients were prescribed 130 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice a day, on days 1-14 of a 21-day cycle. Four treatment-related deaths in the first 24 patients led to a reduction in capecitabine to 850 mg/m2 orally twice a day, days 1-14, for the remainder of the cohort.
The tumor response rate was 35% [95% confidence intervals (CI) 23% to 50%]. All responses were partial; seven of 24 occurred before the capecitabine dose reduction, and eight of 19 after. Median time to tumor progression was 4 months (95% CI 3.1-4.6), and median survival 6.4 months (95% CI 4.6-10). To date, there have been 36 deaths. Four were treatment-related (one infection, two myocardial infarctions, one respiratory failure), and all occurred before the capecitabine dose reduction. Notable grade 4 events from the entire cohort included diarrhea (two patients), vomiting (three), dyspnea (one), thrombosis (two) and anorexia (two). Grade 3 events included nausea (12 patients), diarrhea (12), fatigue (10), abdominal pain (seven), vomiting (six), dyspnea (six), hypokalemia (six), dehydration (five), hypokalemia (five) and infection (four).
Oxaliplatin and capecitabine in combination demonstrates activity in metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia. The lower dose (capecitabine 850 mg/m2 orally twice a day, days 1-14, and oxaliplatin 130 mg/m2 intravenously on day 1) yielded an acceptable toxicity profile and merits further study.
奥沙利铂与卡培他滨的协同联合已显示出对包括结肠癌在内的多种胃肠道癌症具有活性。因此，我们开展了这项II期研究，以测试这种一线联合方案用于食管、胃食管交界和胃贲门转移性腺癌患者的疗效。
招募了43例经组织学或细胞学确诊为上述恶性肿瘤的患者。该队列中东部肿瘤协作组（Eastern Cooperative Oncology Group）体能状态评分为0、1和2的患者分别占47%、51%和2%。中位年龄为61岁（范围32 - 80岁）。所有患者的器官功能均良好。最初，患者在第1天静脉注射130 mg/m²，卡培他滨1000 mg/m²，每天口服两次，在21天周期的第1 - 14天服用。前24例患者中有4例与治疗相关的死亡，导致队列中其余患者的卡培他滨剂量减至850 mg/m²，每天口服两次，第1 - 14天服用。
肿瘤缓解率为35%[95%置信区间（CI）23%至50%]。所有缓解均为部分缓解；24例中有7例在卡培他滨剂量降低之前出现缓解，19例中有8例在剂量降低之后出现缓解。肿瘤进展的中位时间为4个月（95%CI 3.1 - 4.6），中位生存期为6.4个月（95%CI 4.6 - 10）。迄今为止，已有36例死亡。4例与治疗相关（1例感染、2例心肌梗死、1例呼吸衰竭），且均发生在卡培他滨剂量降低之前。整个队列中显著的4级事件包括腹泻（2例患者）、呕吐（3例）、呼吸困难（1例）、血栓形成（2例）和厌食（2例）。3级事件包括恶心（12例患者）、腹泻（12例）、疲劳（10例）、腹痛（7例）、呕吐（6例）、呼吸困难（6例）、低钾血症（6例）、脱水（5例）、低钠血症（5例）和感染（4例）。
奥沙利铂与卡培他滨联合用药对食管、胃食管交界和胃贲门转移性腺癌具有活性。较低剂量方案（卡培他滨850 mg/m²，每天口服两次，第1 - 14天；奥沙利铂130 mg/m²，第1天静脉注射）产生了可接受的毒性特征，值得进一步研究。
Zotero 插件